Pspa bacteria

Disbalancing envelope stress responses was investigated as a strategy for sensitization of Escherichia coli to antimicrobial agents. Seventeen isogenic strains were selected from the KEIO collection with deletions in genes corresponding to the σE , Cpx, Rcs, Bae, and Psp responses. Antimicrobial activity against 20 drugs with different targets was evaluated by disk diffusion and gradient strip tests. Growth curves and time-kill curves were also determined for selected mutant-antimicrobial combinations. An increase in susceptibility to ampicillin, ceftazidime, cefepime, aztreonam, ertapenem, and fosfomycin was detected...

BACKGROUND: Toxin-antitoxin (TA) systems, abundant in prokaryotes, are composed of a toxin gene and its cognate antitoxin. Several toxins are implied to affect the physiological state and stress tolerance of bacteria in a population. We previously identified a chromosomally encoded hok-sok type I TA system in Erwinia amylovora, the causative agent of fire blight disease on pome fruit trees. A high-level induction of the hok gene was lethal to E. amylovora cells through unknown mechanisms...

OBJECTIVE: The evidence shows that previous infection with enteric pathogens is a requirement to develop pSpA. Based on our previous results, variances on regulation of SIgA might influence SpA activity; thus, the aim of this study was to correlate the levels of SIgA, IgA against some enteric bacteria, and IL-17, IL-21, and IL-6 with clinical features in a group of SpA patients. METHODS: Twenty-six pSpA, 20 nr-axSpA, 60 healthy volunteers (HV), and 34 patients with inflammatory bowel diseases (IBD) were included...

Transfer-messenger RNA (tmRNA) is ubiquitous in bacteria, acting as the core component for the trans-translation system that contributes to label the aberrantly synthesized peptides for degradation and to release the stalled ribosomes. Deletion of tmRNA causes a variety of phenotypes related to important physiological processes in bacteria. To illustrate the molecular mechanism of the versatility of tmRNA in aquatic pathogen Aeromonas veronii, we mutated the C-terminal nucleotides of tmRNA (MutmRNA) for encoding a tag containing six histidine residues (His6 tag), so as to capture and enrich the trans-translation substrates from the cell lysates through a Ni2+ -NTA affinity chromatograph...

An effective immunological response in the lungs during a pneumococcal infection is a key factor to the bacteria clearance and prevention of sepsis. In order to develop broad-range pneumococcal vaccines several pneumococcal proteins and strong adjuvants have been investigated. Previously, we constructed a recombinant BCG (rBCG) strain expressing a fragment of PspA (Pneumococcal surface protein A) fused to PdT (detoxified form of pneumolysin). Immunization of mice with a priming dose of rBCG PspA-PdT followed by a booster dose of rPspA-PdT fused protein induced a high antibody response in the serum and protected mice against lethal challenge...

BACKGROUND & AIMS: Dysregulation of the microbiome has been associated with development of complex diseases, such as obesity and diabetes. However, no method has been developed to control disease-associated commensal microbes. We investigated whether immunization with microbial antigens, using CpG oligodeoxynucleotides and/or curdlan as adjuvants, induces systemic antigen-specific IgA and IgG production and affects development of diseases in mice. METHODS: C57BL/6 mice were given intramuscular injections of antigens (ovalbumin, cholera toxin B-subunit, or pneumococcal surface protein A) combined with CpG oligodeoxynucleotides and/or curdlan...

Pneumococcal strains are variably resistant to killing by neutrophil extracellular traps (NETs). We hypothesize that this variability in resistance is due to heterogeneity in pneumococcal surface protein A (PspA), a structurally diverse virulence factor of Streptococcus pneumoniae. Pneumococcal strains showed variability in induction of NETs and in susceptibility to killing by NETs. The variability in susceptibility to NETs-mediated killing of pneumococcal strains is attributed to PspA, as strains lacking the surface expression of PspA were significantly more sensitive to NETs-mediated killing compared to the wild-type strains...

Streptococcus pneumoniae (the pneumococcus) is a human respiratory tract pathogen and a major cause of morbidity and mortality globally. Although the pneumococcus is a commensal bacterium that colonizes the nasopharynx, it also causes lethal diseases such as meningitis, sepsis, and pneumonia, especially in immunocompromised patients, in the elderly, and in young children. Due to the acquisition of antibiotic resistance and the emergence of nonvaccine serotypes, the pneumococcus has been classified as one of the priority pathogens for which new antibacterials are urgently required by the World Health Organization, 2017...

The phage shock protein (Psp) system is a stress response pathway that senses and responds to inner membrane damage. The genetic components of the Psp system are present in several clinically relevant Gram-negative bacteria, including Vibrio cholerae However, most of the current knowledge about the Psp response stems from in vitro studies in Escherichia coli and Yersinia enterocolitica. In fact, the Psp response in V. cholerae has remained completely uncharacterized. In this study, we demonstrate that V. cholerae does have a functional Psp response system...

Streptococcuspneumoniae, or pneumococcus, is a major respiratory-tract pathogen that causes high levels of mortality and morbidity in infants and elderly individuals. Despite the development of various capsular polysaccharide vaccines to prevent pneumococcal disease, it remains epidemic. Pneumococcal surface protein A (PspA) is a highly immunogenic surface protein existing in all strains of S. pneumoniae, and it can elicit immunizing protection against pneumococcal infection. In our previous studies, a fusion protein (PsaA-PspA23), consisting of PspA and pneumococcal surface antigen A (PsaA), displayed greater immunogenicity and provided better protection in mice against S...

Complement is a critical component of antimicrobial immunity. Various complement regulatory proteins prevent host cells from being attacked. Many pathogens have acquired the ability to sequester complement regulators from host plasma to evade complement attack. Here we describe how Streptococcus pneumoniae adopts a strategy to prevent the formation of the C3 convertase, C4bC2a, by the rapid conversion of surface bound C4b and iC4b into C4dg, which remains bound to the bacterial surface but no longer forms a convertase complex...

Streptococcus pneumoniae is an infectious pathogen mainly infecting host bodies through the respiratory system. An effective pneumococcal vaccine would be targeted to the mucosa and provide not only protection against invasive infection but also against colonization in the respiratory system. In the present work, we applied bacterium-like particles (BLPs) as an adjuvant for the development of a PspA mucosal vaccine, in which the PspA protein was displayed on the surface of BLPs. Intranasal immunization with the PspA-BLP pneumococcal vaccine, comprised of PspA2 from pneumococcal family 1 and PspA4 from pneumococcal family 2, not only induced a high level of serum IgG antibodies but also a high level of mucosal SIgA antibodies...

Streptococcus pneumoniae is an important pathogen accounting for a large number of deaths worldwide. Despite the multitude of capsular polysaccharide vaccines used to guard against pneumococcal disease, fatal pneumococcal disease remains epidemic due to the narrow range of protection afforded by the capsular polysaccharide vaccines and rate of change in serotypes. The most promising solution is to develop an improved protein-based vaccine with broad protection. In this study, we tested a bivalent vaccine containing antigens mixed with the fusion protein PsaA-pneumococcal surface protein A (PspA)23 and single protein PspA4, including conserved PsaA and PspA from clades 2, 3, and 4 with coverage for families 1 and 2...

Infectious diseases are the second leading cause of death worldwide, suggesting that there is still a need for the development of new and improved strategies for combating pathogens effectively. Streptococcus pneumoniae is the most virulent bacteria causing pneumonia with high mortality, especially in children and the elderly. Because of the emergence of antibiotic resistance in S. pneumoniae, employing a serotype-independent mucosal vaccine would be the best approach to prevent and treat the diseases caused by S...

Mycobacterium tuberculosis is a global pathogen of significant medical importance. A key aspect of its life cycle is the ability to enter into an altered physiological state of nonreplicating persistence during latency and resist elimination by the host immune system. One mechanism by which M. tuberculosis facilitates its survival during latency is by producing and metabolizing intracytoplasmic lipid droplets (LDs). LDs are quasi-organelles consisting of a neutral lipid core such as triacylglycerol surrounded by a phospholipid monolayer and proteins...

Streptococcus pneumoniae is a major cause of invasive pneumococcal disease, septicemia, and meningitis that can result in high morbidity rates in children under 5 years old. The current polysaccharide-based vaccines can provide type-specific immunity, but a broad-spectrum vaccine would provide greater coverage. Therefore, developing pneumococcal-protein-based vaccines that can extend to more serum types is highly important. In this study, we vaccinated mice via the subcutaneous (s.c.) route with a systemic vaccine that is a mixture of fusion protein PsaA-PspA23 and a single protein, PspA4, with aluminum hydroxide as an adjuvant...

The phage shock protein (Psp) stress-response system protects bacteria from envelope stress through a cascade of interactions with other proteins and membrane lipids to stabilize the cell membrane. A key component of this multi-gene system is PspA, an effector protein that is found in diverse bacterial phyla, archaea, cyanobacteria, and chloroplasts. Other members of the Psp system include the cognate partners of PspA that are part of known operons: pspF||pspABC in Proteobacteria, liaIHGFSR in Firmicutes, and clgRpspAMN in Actinobacteria...

Burden of pneumonia caused by Streptococcus pneumoniae remains high despite the availability of conjugate vaccines. Mucosal immunization targeting the lungs is an attractive alternative for the induction of local immune responses to improve protection against pneumonia. Our group had previously described the development of poly(glycerol adipate-co-ω-pentadecalactone) (PGA-co-PDL) polymeric nanoparticles (NPs) adsorbed with Pneumococcal surface protein A from clade 4 (PspA4Pro) within L-leucine microcarriers (nanocomposite microparticles-NCMPs) for mucosal delivery targeting the lungs (NP/NCMP PspA4Pro)...

OBJECTIVE: Pneumococcal infection caused by Streptococcus pneumoniae is a major upper respiratory tract disease that causes severe illness and mortality. Therefore, it is important to develop safe and effective vaccines to prevent pneumococcal infections. The goal of the study was to investigate the effectiveness of transcutaneous immunization (TCI) for induction of pneumococcal surface protein A (PspA) responses in the upper respiratory tract. METHODS: C57BL/6 mice were transcutaneously immunized with 1 μg of PspA and 2 μg of cholera toxin (CT) six times at weekly intervals and compared with transcutaneously treated controls (PBS alone/PspA alone/CT alone)...

BACKGROUND: Clinical trials of vaccines for children to prevent acute otitis media (AOM) infections caused by the bacteria Streptococcus pneumonia (Spn) are in Phase I. The objective of this study was to use serum antibody measurements to pneumococcal purified protein candidate antigens that occurred after natural "immunization" to predict a correlate of protection response needed following an injectable vaccine against AOM in children. METHODS: 590 nasal and serum samples were collected from 129 healthy children at 6, 9, 12, 15, 18, 24 and 30-36 months of age and when the child developed AOM...